Naltrexone microspheres: in vitro release and effect on morphine analgesiain mice

AIM: To study in vitro release and in vivo effect of four different types o f sustained-release naltrexone microspheres on, morphine analgesia. METHODS : Release of naltrexone from four types of biodegradable micro-spheres was investigated by HPLC. Their antagonist effects on morphine analgesia were o bserved using mouse hot-plate procedure. RESULTS: Poly latide-co-glycolide (PLGA) composition had a remarkable effect on naltrexone release from micro spheres and its antagonism towards morphine analgesia. Two formulations of PLGA 50:50 formulation released more than 80 % of total naltrexone and lost their antagonism by 8 d. The PLGA 75:25 formulation with 20 % and 30 % dru g loadings did not release 95 % of total drug and lose antagonism until 40 d and 30 d, respectively. Increasing the drug loading enhanced naltrexone r elease from microspheres and seemed to shorten the analgesic antagonistic e ffect of naltrexone. CONCLUSION: Antagonism by naltrexone microspheres towa rds morphine analgesia correlates well with the drug release in vitro.